Impaired 11β-hydroxysteroid dehydrogenase type 2 activity in kidney disease disrupts 11-oxygenated androgen biosynthesis.

Context: 11-oxygenated androgens are a group of adrenal-derived steroids that require peripheral activation. In vitro data highlight a putative role for 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) in 11-oxygenated androgen biosynthesis, converting 11β-hydroxyandrostenedione (11OHA4) to 11-ketoandrostenedione (11KA4), the direct precursor of the potent androgen 11-ketotestosterone (11KT). As the kidney is the major site of HSD11B2 expression, we hypothesized that patients with chronic kidney disease (CKD) would have reduced 11-oxygenated androgen biosynthesis due to impaired HSD11B2 activity.

ANCA-associated vasculitis in Ireland: a multi-centre national cohort study.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease. There is a need for interoperable national registries to enable reporting of real-world long-term outcomes and their predictors in AAV. The Irish National Rare Kidney Disease (RKD) registry was founded in 2012.

Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients.

Background: Non-adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to immunosuppressant therapy is a modifiable patient behaviour, and different approaches to increasing adherence have emerged, including multi-component interventions. There has been limited exploration of the effectiveness of interventions to increase adherence to immunosuppressant therapy.

Adrenal insufficiency is common amongst kidney transplant recipients receiving maintenance prednisolone and can be predicted using morning cortisol.

Background: Long-term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTRs), leading to significant cumulative glucocorticoid exposure. The aims of this study are to investigate the prevalence of adrenal insufficiency (AI) in KTRs taking prednisolone and to develop a screening algorithm to identify patients at the highest risk of AI.

Methods: In this cross-sectional cohort study, 67 KTRs receiving prednisolone underwent a short synacthen test (SST) and measurement of cumulative glucocorticoid exposure.

Risk factors and long-term consequences of new-onset diabetes after renal transplantation.

Background: New-onset diabetes after transplant (NODAT) confers risk of diabetes-related complications as well as a threat to graft function and overall patient survival. The reported incidence of NODAT varies from 14 to 37% in renal transplant recipients worldwide; however, NODAT is yet to be studied in the Irish renal transplant population.

Aims: Primary aims of this project were to estimate the incidence, to determine associated risk factors and to assess the long-term consequences of NODAT on graft survival and patient survival in the Irish renal transplant population.

Assessing the discrimination of the Kidney Donor Risk Index/Kidney Donor Profile Index scores for allograft failure and estimated glomerular filtration rate in Ireland's National Kidney Transplant Programme.

Background: The Kidney Donor Risk Index (KDRI)/Kidney Donor Profile Index (KDPI) is relied upon for donor organ allocation in the USA, based on its association with graft failure in time-to-event models. However, the KDRI/KDPI has not been extensively evaluated in terms of predictive metrics for graft failure and allograft estimated glomerular filtration rate (eGFR) outside of the USA.

Methods: We performed a retrospective analysis of outcomes in the Irish National Kidney Transplant Service Registry for the years 2006-13.

Progressive improvement in short-, medium- and long-term graft survival in kidney transplantation patients in Ireland - a retrospective study.

It is often quoted that while short-term graft survival in kidney transplantation has improved in recent years, it has not translated into a commensurate improvement in long-term graft survival. We considered whether this was true of the entire experience of the national kidney transplant program in Ireland. A retrospective analysis of the National Kidney Transplant Service (NKTS) database was undertaken to investigate patient and graft survival for all adult first deceased donor kidney transplant recipients in Ireland, 1971-2015.

Monogenic causes of chronic kidney disease in adults.

Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD.

Direct-Acting Oral Anticoagulants as Prophylaxis Against Thromboembolism in the Nephrotic Syndrome.

We report 2 cases of apixaban use as prophylaxis against thromboembolism in the nephrotic syndrome (NS), and review the existing literature on direct-acting oral anticoagulant (DOAC) use in this scenario. Our cases appear to be the first reported use of apixaban as prophylaxis against thromboembolism in NS. We report our systematic review of the existing literature on direct-acting oral anticoagulant (DOAC) use in NS, and discuss theoretical issues relevant to their therapeutic use in this clinical scenario.

A suspected case of autoinduction of voriconazole metabolism in a patient with cerebral aspergillosis.

Objective: This study aims to report a case of accelerated metabolism of voriconazole in a patient with cerebral aspergillosis.

Case Summary: A 36-year-old woman developed cerebral aspergillosis after immunosuppressive treatment for suspected atypical hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. She was treated with voriconazole using therapeutic drug monitoring to guide dosing.

Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.

Background: Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes.

The Irish living kidney donor program - why potential donors do not proceed to live kidney donation?

Background: Living donation is not only a method to increase access to kidney transplantation but can also offer superior outcomes. We report the experience of the living donor (LD) program in the Republic of Ireland and explore reasons why potential donors do not proceed to live donation.

Methods: Retrospective cohort study of all potential donors from January 2000 to March 2014 who presented wishing to undergo donor work-up and their subsequent outcomes.

Tacrolimus trough-level variability predicts long-term allograft survival following kidney transplantation.

Aims: The purpose of this study is to investigate tacrolimus trough-level variability from 3 to 12 months following transplantation and its association with allograft survival in renal transplant recipients.

Materials And Methods: In this observational cohort study, tacrolimus trough-level variability was used as the predictor of all-cause allograft failure (defined as return to dialysis) and patient survival (all-cause mortality).

Results: In total, 394 transplants were included in the analysis.

The influence of socioeconomic status on patient survival on chronic dialysis.

Socioeconomic status (SES) has been linked to worse end-stage kidney disease survival. The effect of SES on survival on chronic dialysis, including the impact of transplantation, was examined. A retrospective, observational study investigated the association of SES with dialysis patient survival, with censoring at time of transplantation.

rhErythropoietin-b as a tissue protective agent in kidney transplantation: a pilot randomized controlled trial.

Background: Extended criteria donor (ECD) and donation after circulatory death (DCD) kidneys are at increased risk of delayed graft function (DGF). Experimental evidence suggests that erythropoietin (EPO) attenuates renal damage in acute kidney injury. This study piloted the administration of high dose recombinant human EPO-beta at implantation of ECD and DCD kidneys, and evaluated biomarkers of kidney injury post-transplant.

Influence of socioeconomic status on allograft and patient survival following kidney transplantation.

Aim: Whether socioeconomic status confers worse outcomes after kidney transplantation is unknown. Its influence on allograft and patient survival following kidney transplantation in Ireland was examined.

Methods: A retrospective, observational cohort study of adult deceased-donor first kidney transplant recipients from 1990 to 2009 was performed.

Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients.

The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these limitations, we used microarrays and conventional methods to investigate rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant from North American and European centers. Using conventional methods, we diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR, and 28 mixed (89 designated borderline).

Erythropoietin has a restorative effect on the contractility of arteries following experimental hypoxia.

Introduction: The aim of this study was to investigate the effect of erythropoietin on vascular contractility using an in vitro model of hypoxia replicating the hypoxic environment of blood vessels and surrounding adipose tissue in obesity.

Methods And Results: Pharmacological in vitro studies were carried out on small mesenteric arterial segments from male Wistar rats with and without perivascular fat and endothelium. Contractile responses were investigated by wire myography under normoxia, experimental hypoxia ± erythropoietin and l-NNA.

Molecular phenotypes of acute kidney injury in kidney transplants.

Little is known regarding the molecular phenotype of kidneys with AKI because biopsies are performed infrequently. However, all kidney transplants experience acute injury, making early kidney transplants an excellent model of acute injury, provided the absence of rejection, because donor kidneys should not have CKD, post-transplant biopsies occur relatively frequently, and follow-up is excellent typically. Here, we used histopathology and microarrays to compare indication biopsies from 26 transplants with acute injury with 11 pristine protocol biopsies of stable transplants.

Encapsulating peritoneal sclerosis following renal transplantation despite tamoxifen and immunosuppressive therapy.

Encapsulating peritoneal sclerosis (EPS) is a rare disease in patients who have undergone peritoneal dialysis (PD). We report a case of EPS following renal transplantation that highlights important clinical issues. Initially, a presumptive diagnosis of EPS was made following surgical and pathological findings at the time of cholecystectomy.

Nutritional management of patients undergoing surgery following diagnosis with encapsulating peritoneal sclerosis.

Background: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). Gastrointestinal (GI) symptoms affect appetite and dietary intake. Adequate nutrition is especially important if surgical interventions are required.